Interaction of Early Growth Response Protein 1 (Egr-1), Specificity Protein 1 (Sp1), and Cyclic Adenosine 3'5'-Monophosphate Response Element Binding Protein (CREB) at a Proximal Response Element Is Critical for Gastrin-Dependent Activation of the Ch

Raychowdhury R; Schafer G; Fleming JRosewicz SWiedenmann BWang TCHocker M

首页> 外文期刊>Molecular Endocrinology >Interaction of Early Growth Response Protein 1 (Egr-1), Specificity Protein 1 (Sp1), and Cyclic Adenosine 3'5'-Monophosphate Response Element Binding Protein (CREB) at a Proximal Response Element Is Critical for Gastrin-Dependent Activation of the Ch

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Interaction of Early Growth Response Protein 1 (Egr-1), Specificity Protein 1 (Sp1), and Cyclic Adenosine 3'5'-Monophosphate Response Element Binding Protein (CREB) at a Proximal Response Element Is Critical for Gastrin-Dependent Activation of the Ch

机译：Interaction of Early Growth Response Protein 1 (Egr-1), Specificity Protein 1 (Sp1), and Cyclic Adenosine 3'5'-Monophosphate Response Element Binding Protein (CREB) at a Proximal Response Element Is Critical for Gastrin-Dependent Activation of the Ch

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Recently, binding of specific protein 1 (Sp1) and cAMP response element binding protein (CREB) to a GC-rich element at -92/-62 has been identified as a critical step in gastrin-dependent regulation of the chromogranin A (CgA) gene in gastric epithelial cells. Here we demonstrate that binding of early growth response protein 1 (Egr-1) to the distal part of the -92/-62 site is also required for gastrin-dependent CgA transactivation. Gastrin elevated cellular and nuclear Egr-1 levels in a time-dependent manner and also increased Egr-1 binding to the CgA -92/-73 region. Disruption of this site reduced gastrin responsiveness without influencing basal promoter activity, while loss of Sp1 and/or CREB binding sites diminished basal and gastrin-stimulated CgA promoter activity. Ectopic Egr-1 overexpression potently stimulated the CgA promoter, whereas coexpression of Egr-1 with Sp1 and/or CREB resulted in additive effects. Functional analysis of Sp1-, Egr-1-, or CREB-specific promoter mutations in transfection studies confirmed the tripartite organization of the CgA -92/-62 element. Signaling studies revealed that MAPK kinase 1 (MEK1)/ERK1/2 cascades are critical for gastrin-dependent Egr-1 protein accumulation as well as Egr-1 binding to the CgA promoter. Our studies for the first time identify Egr-1 as a nuclear target of gastrin and show that functional interplay of Egr-1, Sp1, and CREB is indispensable for gastrin-dependent CgA transactivation in gastric epithelial cells.

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《Molecular Endocrinology》 |2002年第12期|2802-2818|共17页
作者
Raychowdhury R; Schafer G; Fleming JRosewicz SWiedenmann BWang TCHocker M;
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Medizinische Klink mit Schwerpunkt Gastroenterologie, Hepatologie, Endokrinologie und Stoffwechsel (G.S., S.R., B.W., M.H.), Universitatsklinikum Charite, Campus Virchow-Klinikum, Humboldt Universitat, 13353 Berlin, Germany.;

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正文语种英语
中图分类内分泌腺疾病及代谢病;内分泌生理学;
关键词
chromogranin A; Gastrin; DNA-Binding Protein; Cyclic AMP-Responsive; Response Elements; DNA结合蛋白质; 环AMP反应性; 反应元件;

Interaction of Early Growth Response Protein 1 (Egr-1), Specificity Protein 1 (Sp1), and Cyclic Adenosine 3'5'-Monophosphate Response Element Binding Protein (CREB) at a Proximal Response Element Is Critical for Gastrin-Dependent Activation of the Ch

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